Triple Therapy for CAR T-Related Guillain-Barré Syndrome: A Case Report

BCMA-directed chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized treatment of relapsed/refractory (R/R) multiple myeloma but can be complicated by delayed neurotoxicities that are distinct from immune effector cell neurotoxicity syndrome (ICANS). Unrestrained lymphocytosis, possibly reflecting CAR T-cell expansion, is the only identified predictor.¹ These non-ICANS neurotoxicities (NINTs) span cranial nerve palsies, parkinsonism, and others for which management consensus is emerging.² Guillain-Barré syndrome (GBS) is far rarer and, alongside other polyneuropathies, accounts for only 7.5% of NINT events.³ No treatment consensus exists: intravenous immunoglobulin (IVIG) and steroids are ineffective,⁴ and cyclophosphamide has been used with variable success.⁵

A 39-year-old woman with R/R IgG-lambda plasma cell leukemia received ciltacabtagene autoleucel, complicated by grade 1 cytokine release syndrome but no ICANs. She received steroids for unrestrained lymphocytosis on day 10 and had a second, lower peak on day 22. By day 28, she developed progressive lower-extremity numbness and weakness; EMG and CSF findings supported demyelinating GBS. She also had pancytopenia and evidence of evolving immune-effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. PET-CT showed diffuse FDG-avid lymphadenopathy, and a large granular lymphocytic (LGL) population was identified in the peripheral blood and lymph nodes, but not myeloma cells. Correlative analyses showed T-cell oligoclonality, and an analytically validated WPRE-based PCR showed high CAR T-cell fractions in CSF, lymph nodes, and blood. She received novel triple therapy—IVIG, pulse steroids, and ruxolitinib—with LGL and CAR-T contraction, functional strength recovery, and resolution of pancytopenia and previously FDG-avid lesions on repeat PET-CT.

This case highlights the novel use of biomarker-guided triple therapy for GBS after CAR-T. Oligoclonal LGL expansion in blood and lymph nodes with high CAR T-cell fractions at symptom onset, and their resolution after treatment, offer mechanistic insight for diagnostic and response monitoring in this devastating entity.